Tuesday, July 12, 2011

Genetic Effect on Obesity Increases with Obesogenic Environment

Imagine that there were people with a genetic predisposition to asthma. Many different genes are involved – the more ‘asthma’ genes you have – the more severe your asthma.

Now imagine that people with a high genetic risk, a moderate genetic risk, a substantial genetic risk and a severe genetic risk for asthma were all living out in cottage country, where there is clean air with no air-borne dust or pollutants. Only those few individuals unfortunate enough to have ‘severe’ genetic risk would have asthma – everyone else would be perfectly fine.

Researchers studying the relationship between asthma and genetics in cottage country would find that in most people genes have no effect on asthma symptoms and only in people with very severe asthma would there appear to be some genetic influence.

Now imagine that a busy highway is built straight through that community with lots of heavy car and truck traffic that significantly reduces air quality.

Now, even those with low genetic risk will start wheezing, those with moderate risk will start coughing, those with substantial risk will no longer be able to do heavy work outside, and those with the most severe risk will be confined to their beds under an oxygen tent.

Suddenly, researchers studying this community, will find that there is a close relationship between genetic risk and asthma symptoms – indeed, the difference between those who have no, some, moderate, substantial or severe asthma can almost entirely be explained by genetics. In fact, in those with any symptom of asthma – the entire ‘variance’ will be found to be almost completely attributable to their genetic risk – suddenly genes become the most important determinant of who has symptoms and who doesn’t!

Not surprisingly, exactly the same is true with obesity, according to a large twin study by Benjamin Rokholm and colleagues from the University of Copenhagen, published in the latest edition of PLoS One.

The researchers examined data on 15,017 monozygotic and dizygotic twin pairs born between 1931 through 1982.

Using classical twin-study methodologies, they found that the additive genetic variation was positively and significantly associated with obesity prevalence and the mean of the BMI distribution.

In other words, as the prevalence of obesity, prevalence of overweight and the BMI mean increased, so did the ‘genetic’ variation in BMI.

As in the theoretical asthma example, these findings are consistent with the notion that variations in genes related to body fatness are more important and lead to greater weight gain under the influence of an obesity-promoting environment.

While this study points to the idea that we need to get serious about tackling the environmental drivers of obesity, it also means that in the meantime, the existing environmental factors will disproportionately affect those with the greatest genetic risk.

So, while everyone is sedentary, get too little sleep, is stressed out and, therefore, eats too many calories – those with the greatest genetic load will gain the most weight, while those with no genetic risk will be just fine (we all know these people).

From a health services perspective this means that, while we wait for policy makers to pass new laws that will help reverse the many obesogenic factors in our current environment (which is likely to take as long as it will take them to reverse global warming), we need to provide appropriate help and care to those who are suffering the consequences from having chosen the wrong parents.

Genetics does not mean you cannot do anything about it – it just means that those with a greater genetic risk need to do much more (often with professional help) to manage their weight than those who happen to have lower genetic risk.

Of course it is also not helpful to tell those with the highest genetic risk to simply live like those with no genetic risk – because that is already exactly what they are doing – unfortunately, they have to do far more!

Sure, the best way to get our severe asthma patient out of the oxygen tent would be to shut down the highway (or mandate cleaner cars) – in the meantime, however, let’s make sure there’s enough oxygen flowing into the tent for those who need it.

AMS
Edmonton, Alberta

Rokholm B, Silventoinen K, Angquist L, Skytthe A, Kyvik KO, & Sørensen TI (2011). Increased Genetic Variance of BMI with a Higher Prevalence of Obesity. PloS one, 6 (6) PMID: 21738588

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17 Responses to “Genetic Effect on Obesity Increases with Obesogenic Environment”

  1. Karen says:

    This makes absolute sense to me, as both the parent of a moderately asthmatic child, and a person who has struggled with obesity all my life. My daughter does well in winter, when the air is less muggy and dirty; but at this time of year, in the smoggy Ottawa summer, she suffers.

    Currently, I’m 10 years post-RNY, and while I am careful about food and eat less than 1200 cal/day, I’m finding the weight has been creeping back on–technically I’m a “weight loss surgery success,” but in reality the struggle never ended. I’m not sure what my next steps will be, but your comment about having to work much harder just to stay in the same place as a non-genetically obese person really hit home with me.

  2. Louise Aspden says:

    Yes. This does make perfect sense to me to. Thank you for making it so clear to us “lay people”! I have a son with asthma and have struggled with managing my weight my whole adult life. Karen is right – it is never over. I have been “maintaining” for three years now at I still struggle with making healthy choices every day. I have learned that over time, slowly new habits form to make it easier. The good thing is we can overcome obesity by changing our lifestyle, I wish the same could be said for asthma.

  3. Anne says:

    Are the tests to tell if an individual is genetically prone to obesity only available in research labs right now, or are these tests currently in use in any medical or clinical settings?

  4. Janis says:

    YES. What’s considered a “cause” of something really depends on how you ask. There’s probably individual differences in how a cholera bug attacks and damages each individual body … but when John Snow said that the Broadwick epidemic was caused by a water pump, he was right. What causes it in one person is not the same as when one asks what’s causing an epidemic.

  5. DeeLeigh says:

    Anne, they don’t even understand the mechanisms that make some people heavier than others, let alone all the genes that would contribute to the different ways our bodies function in relation to weight, build, energy levels, appetite and metabolism.

    (Hope it’s okay to jump in with this, but if they’d identified enough fat genes to categorize people as ‘genetically prone to obesity,’ I’m pretty sure I would have heard about it)

  6. Giridharan says:

    Well put Sharma..And this is what we are trying to prove in the animal expriment we are about to embark on.We have selected 4 strains of rats with gradation of physical activity (Low to high) and gradation of fat per 100g body weight.Each will be challenged with high and low macronitrients and their effect on body weights will be assessed through microarray and epigenitic pathways.We beleive that this will give us a clue to the obesogenic area of the genome that will be activated and will discern the role of nature and nurture in the outcome of the phenotype, i.e., obesity.

  7. Paulette says:

    This makes more sense that almost anything else I have read on this subject. Yes indeed, a person with high genetic risk factors for heart disease doesn’t automatically develop heart disease, but its good to know your family history so you can take whatever measures you need to in order to maintain good health. Without knowing all the variables that can contribute it is probably a good idea to cast your eyes backward in your family. I recall my mother saying that my great grandmother was a heavy woman. She grew up raised her family and lived her life farming – not a sedentary lifestyle by any means. gives me a better understanding why I have to remain vigilant (about intake/ and activity) in general just to maintain where I am. (Which is still in the obese range although for the last 5 years lower in that range than the preceding 3)

  8. Janis says:

    Quick comment:

    So, while everyone is sedentary, get too little sleep, is stressed out and, therefore, eats too many calories – those with the greatest genetic load will gain the most weight, while those with no genetic risk will be just fine (we all know these people).

    In some cases, I think “no genetic risk” includes people who tend not to overeat in the presence of stress. Or who tend to undereat, as I do. I tend to react to stress or physical discomfort by not wanting to eat. I’m not denying hunger, I just find it really awful to put food on an upset stomach. I also detest feeling too full. This may be genetic, but it’s a genetic tendency to NOT eat too many calories, which short-circuits your “therefore” up there right out of the gate and already exerts a filtering mechanism on the “everyone.”

    Seriously. If I forget to have dinner the night before because I was busy, I will make it to lunchtime the next day, feel acidy in my stomach, think, “I feel sick, I can’t eat,” and then have to consciously remind myself, “You feel sick because you didn’t eat dinner, dummy. Go eat something and you’ll feel better.” And it had still better be something fresh and light, or else I’ll become nearly comatose while digesting it.

  9. Janis says:

    At least some of the genetics has been worked out and mentioned here

  10. Keith Grimaldi says:

    I wish this level of understanding was more widely present among the medical community, and the press! But also amongst genetecists – the funding is way to far off balance in favour of genetics compared to environmental causes. Of course the ideal would be to look for both at the same time, it’s the only real way to make any sense of things (http://bit.ly/mPzcXr and http://bit.ly/bB2Efd)

    We have to accept the good and the bad of our genes. I was speaking to a colleague from Brazil a while ago, while he was constantly battling his weight, he was not miserable, he said that if he did not have these fat storing thrifty genes he would not be here, his ancestors would not have survived the famines!

    In the end it’s like going to the beach, i hate having to put on the sunscreen several times during the day, I don’t like that I get burnt either – but I do like that I made plently of vitamin D when I was growing up in cold grey England!

  11. ABetterWay says:

    What about those of us who are not sedentary, get enough sleep, are not overly stressed, and do not eat too many calories? Will we be okay too? Of course we will! And we will be regardless of our genetic and environmental risk profile. Herein lies the solution: Everyone has to deal individually with their own unique genetic and environmental situation. Some will need to work much harder than others, which isn’t exactly fair, but that’s just the way it is!

  12. Dana says:

    Of course, part of the environment that’s promoting obesity is people’s belief that obesity is about eating more and exercising less. When you people get past that and start looking at the actual scientific evidence, we might get somewhere.

    There are fat triathletes and marathon runners. I challenge anyone here to prove that any of them are “underactive.” There are slender couch potatoes. No one gets on their cases about how much they move.

    It’s true that someone with a weight issue is going to have to work harder to get to a normal weight. But the work is not in the amount eaten or the amount moved. The work is in finding out why the obesity happened and actually solving the problem. Is your fasting insulin too high? Are you not getting enough of nutrients you need? Is your thyroid wonky? You have to have enough knowledge of the human body to even be able to ask these questions, you have to have the curiosity to want to find out the answers, and you have to have the fortitude to follow through all the way to the end. Not everyone can measure up. That’s also true of slender people. How many skinnies have you ever met with cancer or some other disease who just gave up and did whatever their docs told them to do and died anyway?

    I’m tired of seeing “experts” not even bothering to get to the bottom of the issue, they’re off in the lab looking at genetics when genetics apparently *weren’t* a problem once upon a time, and meanwhile they’re blaming the fat people. No, it’s not the fat people’s fault. It’s YOUR fault, for being too lazy or greedy (after all, obese people make a LOT of money for *somebody* out there–diet gurus, statin drug makers, etc.) to find the right answers after you have positioned yourselves as smarter than the rest of us.

    Karen: My dear God, woman. 1200 calories a day is STARVATION. You’re not a bad person–you are malnourished! You can’t do anything now about the way they mutilated you. You need to warn others who are considering the surgery. That is the best way now that you can make sense of what’s been done to you and make it all worthwhile. I am so sorry.

  13. Thorkild IA Sørensen says:

    Thanks, Arya, for promoting our study so nicely. Benjamin is right now finalising another paper further supporting the evience for this interplay between the genetic predisposition and the obesogenic environment. Wait and see.

  14. Thorkild IA Sørensen says:

    Arya, I wouldn’t give your comment on the study just one star and a rating of just +1 – how do I increase it? Thanks.

  15. Bill Graber says:

    I agree with the genetic model. I think that this can also be applied to the effect of the gastric bypass operation. I thnk the operation can be looked at as a genetic operation. It changes the enviroment of the gut (which is connected the brain) , some genes are applified, some are turned on ,some turned off. And genetics also determmines a patients response or suseptability to the operation (change in environment)

  16. Jennifer Morrison says:

    Dr.. Sharma-true-true-true-but nothing has been mentioned on the effect of hysterectomy,and the function of hormone sensitive lipase post hysterectomy.Many women(incl. Myself)gain weight post hysterectomy.Why??when I was underweight pre-surgery,and always normal-but mostly underweight pre-surgery(50+ years)
    Dr. Theron Randolph mentions food addiction as a form of food “allergy”-in that alcoholics crave alcohol because they are “allergic” to wheat,yeast,sugar etc.-the same way I “crave” toast-:))-JM/

  17. Dagny Kight says:

    Happen to find this older post—I want to stand up and CHEER! I base a lot of my writing and work on this and I wrote a book about this because it’s ONLY LOGICAL. Our culture readily accepts that some people are naturally thin with a natural low interest in food and yet we insist that overweight is attributable only to poor judgment, lack of discipline, self-loathing… And the answer? Just THINK LIKE A THIN PERSON! Because we’re supposed to assume people who’ve been thin all their lives are paragons of good judgment and discipline!

    I own life is an example of this. My mother has always been tiny and my brother is just as slim. My father and his whole family are large people and so am I. My dad and I always struggled with our cravings; my mom and brother could take it or leave it.

    Dr. Sharma you’ve really nailed it when you point out that in today’s obesogenic environment, some of us have a tougher job to do to control our weight! And some people simply don’t…Every bell curve has two ends.

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